先天性眼外肌纤维化伴胼胝体发育不良一家系基因突变筛查  

The gene mutation screening of a family with congenital fibrosis of the extraocular muscles associatedwith corpus callosum agenesis

作　　者：张俊涛[1,2] 周炼红[1] 查云飞 刘甜[1] 田明星[1] 袁静[1] 邢怡桥[1] 

机构地区：[1]武汉大学人民医院眼科,430060 [2]湖北省襄阳市中心医院,441021 [3]放射科

出　　处：《中华眼科杂志》2013年第7期621-626,共6页Chinese Journal of Ophthalmology

摘　　要：目的筛查先天性眼外肌纤维化综合征（CFEOM）伴胼胝体发育不良一家系的致病基因。方法对收集到的先天性眼外肌纤维化综合征伴胼胝体发育不良一家系（3代共11例，其中4例发病）进行临床研究以及头颅和眼眶部的MRI检查；然后采用聚合酶链反应扩增产物直接测序的方法对该家系中4例发病者TUBB3基因进行突变检测，以家系中的4例健康者和100例无血缘关系的正常人作对照。结果该家系符合常染色体显性遗传，分型属于CFEOM3型；家系中的发病者均检测出TUBB3突变c．1249G〉A（p．Asp417Asn），突变位于外显子4，导致野生型基因编码的天冬氨酸（asparticacid，Asp或D）被天冬酰胺（asparagine，Asn或N）取代。家系中未发病者和无血缘关系的正常人未检出该突变。结论先天性眼外肌纤维化3型伴有胼胝体发育不良的家系成员出现TUBB3基因突变c．1249G〉A（p．Asp417Asn），可能是导致该CFEOM3家系的主要病因。Objective To identify TUBB3 gene mutations in a Chinese family with congenital fibrosis of the extraocular muscle associated with corpus callosum agenesis. Methods We have found a family with CFEOM associated with coq3us callosmn agenesis, including 4 affected individuals in three generations of 11 familial members. 4 affected individuals were sequenced by direct TUBB3 sequencing, 4 inaffected individuals in the family and 100 cases of unrelated normal person as a control. Results This family is in line with Mendelian autosomal dominant inheritance. Clinical manifestations belongs to CFEOM3. All affected individuals were detected with TUBB3 c. 1249G 〉 A mutation, the mutation is in exon 4, resulting in wild-type gene encoding the Aspartic acid （ Asp or D ） replaced, by Asparagine （Asn or N ）. Conclusion Our study supports that TUBB3 gene mutation c. 1249G 〉 A （p. Asp417Asn ）, is the underlying molecular pathogenesis of this family with CFEOM3.

关 键 词：纤维化 眼疾病 遗传性 眼球运动障碍 胼胝体发育不全 微管蛋白 突变 

分 类 号：R777.4[医药卫生—眼科]